CAMBRIDGE, Mass.--(BUSINESS WIRE)--Editas
Medicine, a transformative genome editing company, today announced
the publication of new data highlighting novel approaches to improve the
specificity of CRISPR/Cas9 genome editing technology. The data are
presented in two papers independently co-authored by company co-founders
Keith Joung, M.D., Ph.D. and David Liu, Ph.D. in the current online
edition of Nature Biotechnology.1,2

“Our understanding of CRISPR/Cas9 genome editing technology and how it
may be applied for therapeutic use continues to mature, and together,
these findings highlight critical advances that improve the specificity
of the CRISPR/Cas9 system,” said Kevin Bitterman, Ph.D., interim
president, Editas Medicine. “Each scientific advance contributes to
Editas’ mission of refining and translating genome editing technology
into therapeutics that will make a meaningful difference for patients.”

The paper
co-authored by Dr. Joung, associate chief of pathology for research
and associate pathologist at Massachusetts General Hospital and
associate professor of pathology at Harvard Medical School,
characterizes the development and optimization of a next-generation,
dimerization-dependent CRISPR-based nuclease technology platform that
shows substantially improved genomic specificities. The cleavage
activity of dimeric RNA-guided dead Cas9 (dCas9)-FokI Nucleases, named
RFNs, depends on the binding of two guide RNAs (gRNAs) to DNA with a
defined spacing and orientation. The published findings show robust
activities compared to monomeric wild-type Cas9 nucleases and nickases,
in addition to improved genomic specificities with no evidence of
unwanted mutagenesis at off-target sites.

The paper
co-authored by Dr. Liu, Howard Hughes Medical Institute investigator
and professor of chemistry and chemical biology at Harvard University,
presents a similar approach to engineering a dimerization-dependent
Cas9-FokI nuclease fusion, named fCas9, with improved specificity. The
fusion protein requires the simultaneous DNA binding and association of
two FokI-dCas9 monomers to cleave DNA. The results show that the
engineered FokI-dCas9 modified target DNA sites with efficiency
comparable to that of nickases, but with greater than 140-fold higher
specificity than wild-type Cas9 in human cells. The specificity of fCas9
was at least four-fold higher than that of paired nickases at human
genome loci with highly similar off-target sites elsewhere in the
genome. Additionally, unwanted binding was reduced further by the
requirement that only sites flanked by two gRNAs approximately 15 or 25
base pairs apart are cleaved.

About Genome Editing

Following an explosion of high-profile publications on CRISPR/Cas9 and
TALENs, genome editing has emerged as one of the most exciting new areas
of scientific research. These recent advances have made it possible to
modify, in a targeted way, almost any gene in the human body with the
ability to directly turn on, turn off or edit disease-causing genes.
Editas Medicine’s five founders have published much of the foundational
work that has elevated genome editing technology to a level where it can
now be optimized and developed for therapeutic use.

CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9
(CRISPR-associated protein 9) and TALENs (transcription activator-like
effector nucleases) comprise novel gene editing methods that overcome
the challenges associated with previous technologies. Early published
research on CRISPR/Cas9, coupled with a growing body of work on TALENs,
suggests the potential to pursue therapeutic indications that have
previously been intractable to traditional gene therapy, gene knock-down
or other genome modification techniques. The CRISPR/Cas9 system, the
most recent and exciting approach to emerge, acts by a mechanism in
which the Cas9 protein binds to specific RNA molecules. The RNA
molecules guide the Cas9 complex to the exact location in the genome
that requires repair. CRISPR/Cas9 uniquely enables highly efficient
knock-out, knock-down or selective editing of defective genes in the
context of their natural promoters, unlocking the ability to treat the
root cause of a broad range of diseases.

About Editas Medicine

Editas Medicine is a transformative genome editing company founded by
five world leaders in the fields of genome editing, protein engineering,
and molecular and structural biology, with specific expertise in
CRISPR/Cas9 and TALENs technologies. The company’s mission is to
translate its genome editing technology into a novel class of human
therapeutics that enable precise and corrective molecular modification
to treat the underlying cause of a broad range of diseases at the
genetic level. Editas Medicine was launched in November 2013 with
funding from Flagship Ventures, Polaris Partners and Third Rock Ventures
with participation from Partners Innovation Fund. For more information,
visit www.editasmedicine.com.